Kynurenine Pathway Activation in Human African Trypanosomiasis.
J Infect Dis
; 215(5): 806-812, 2017 03 01.
Article
en En
| MEDLINE
| ID: mdl-28013248
ABSTRACT
Background:
The kynurenine pathway of tryptophan oxidation is associated with central nervous system (CNS) inflammatory pathways. Inhibition of this pathway ameliorates CNS inflammation in rodent models of the late (meningoencephalitic) stage of human African trypanosomiasis (HAT). In this study, we evaluate whether the kynurenine pathway is activated in clinical HAT and associated with CNS inflammatory responses.Methods:
We measured cerebrospinal fluid (CSF) tryptophan and kynurenine metabolite concentrations in patients infected with Trypanosoma brucei rhodesiense, using liquid chromatography-mass spectrometry.Results:
Kynurenine concentration in CSF was increased in both the early and late stages of disease, with a progressive increase in tryptophan oxidation associated with stage progression. Kynurenine pathway activation was associated with increases in neuroinflammatory markers, but there was no clear relationship to neurological symptoms.Conclusions:
CNS kynurenine pathway activation occurs during HAT, including cases prior to the current diagnostic cutoff for late-stage infection, providing evidence for early CNS involvement in HAT. Metabolite data demonstrate that the kynurenine-3-monooxygenase and kynurenine aminotransferase branches of the kynurenine pathway are active. The association between tryptophan oxidation and CNS inflammatory responses as measured by CSF interleukin 6 (IL-6) concentration supports a role of kynurenine metabolites in the inflammatory pathogenesis of late-stage HAT.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tripanosomiasis Africana
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Triptófano
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Quinurenina
Tipo de estudio:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Adolescent
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Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Infect Dis
Año:
2017
Tipo del documento:
Article
País de afiliación:
Reino Unido